A ubiquitous disordered protein interaction module orchestrates transcription elongation

0548921 - ÚOCHB 2022 RIV US eng J - Journal Article
Čermáková, Kateřina - Demeulemeester, J. - Lux, Vanda - Nedomová, Monika - Goldman, S. R. - Smith, E. A. - Srb, Pavel - Hexnerová, Rozálie - Fábry, Milan - Mádlíková, Marcela - Hořejší, Magdalena - Rijck, J. D. - Debyser, Z. - Adelman, K. - Hodges, H. C. - Veverka, Václav
A ubiquitous disordered protein interaction module orchestrates transcription elongation.
Science. Roč. 374, č. 6571 (2021), s. 1113-1121. ISSN 0036-8075. E-ISSN 1095-9203
R&D Projects: GA ČR(CZ) GA19-14360S; GA MŠMT(CZ) LO1304; GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963 ; RVO:68378050
Keywords : mediator subunit med26 * N-terminal domain * structural characterization
OECD category: Biochemistry and molecular biology
Impact factor: 63.832, year: 2021
Method of publishing: Limited access
https://doi.org/10.1126/science.abe2913

During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation complex, elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other factors. Using nuclear magnetic resonance, live-cell microscopy, and mass spectrometry, we revealed the structural basis for these interactions and found that TND-TIM sequences were necessary and sufficient to induce strong and specific colocalization in the crowded nuclear environment. Disruption of a single TIM in IWS1 induced robust changes in gene expression and RNAP2 elongation dynamics, which underscores the functional importance of TND-TIM surfaces for transcription elongation.
Permanent Link: http://hdl.handle.net/11104/0324967


Research data: Zenodo, Zenodo, Zenodo